Fibromyalgia syndrome is a chronic disease involving widespread pain, stiffness and tenderness in musculoskeletal-related tissues including muscles, tendons and ligaments (Bennett, 2009). Patients with fibromyalgia show sleep disturbances, fatigue, anxiety and/or fibrofog. Fibrofog encompasses the inability to concentrate, memory loss and depression. Fibromyalgia occurs in approximately 2% of the United States general population with a higher incidence in women (3.4%) compared to men (0.5%) (Mease, 2005; Arnold et al., 2006).
The core symptom of fibromyalgia is the widespread pain described as arising from muscle and joints (Bennett, 2009). Many patients with fibromyalgia have tender skin. The pain typically increases and decreases in intensity with flares accompanying unusual exertion, prolonged inactivity, soft tissue injuries, surgery, poor sleep, cold exposure, long car trips and stress. Pain is predominately axial in location but can also occur in hands and feet.
Fatigue is a common symptom for fibromyalgia patients. Fatigue while used interchangeably with sleepiness has been described as a weariness of mind and body that impairs productivity and enjoyment of life (Bennett, 2009). Treatment with antidepressants results in only a modest improvement of fatigue suggesting that there is more to the fatigue symptom than depression. Increased restorative sleep is not sufficient alone to reduce fatigue.
Sleep patterns are commonly disturbed in patients with fibromyalgia (Bennett, 2009). There are issues with sleep initiation and sleep maintenance but patients feel tired when they awaken thus excessive daytime sleepiness results in greater incompatibility with daily functioning than initiation and maintenance of sleep.
Tenderness is typically reported by patients with fibromyalgia where there is sensitivity to touch and pain is experienced even after minor contact (Bennett, 2009). The duration of widespread pain must be of at least three months and tenderness must occur at 11 or more of 18 specific tender spots in order to be classified as fibromyalgia (Mease, 2005; Arnold et al., 2006). In addition, difficulties with memory, concentration and dual tasking are reported issues by fibromyalgia patients.
Fibromyalgia has been shown to be comorbid with bipolar disorder, major depressive disorder, any anxiety disorder, any eating disorder and any substance abuse disorder (Arnold et al, 2006). These diseases may share underlying pathophysiological links and treatment should be chosen with comorbid presenting features in mind.
While the etiology of fibromyalgia is unknown, there is evidence to suggest some abnormalities in central monoaminergic neurotransmission including serotonin and norepinephrine systems (Verdu et al., 2008). Tricyclic antidepressants (TCAs) and SNRIs have been explored as treatment for fibromyalgia. TCAs including amitriptyline, and cyclobezaprine showed modest efficacy with improvements in self-ratings of pain, stiffness, fatigue, sleep and tenderness. Limited and inconsistent results were obtained for SRIs included fluoxetine and citalopram. Positive results were obtained for SNRIs including duloxetine and milnacipran with better improvement in tenderness compared to TCAs and these compounds were specifically approved for fibromyalgia treatment by the FDA in 2007 and 2009, respectively.
Antidepressants used to treat fibromyalgia show adverse reactions in a significant percent of patients (Verdu et al., 2008). It has been shown that progressive introduction of antidepressants increased tolerability. TCAs show mouth dryness, constipation and urinary and bowel emptying difficulties; effects associated with anticholinergic properties. Sedation, drowsiness and orthostatic hypotension are also common. Common side effects of SRI are associated with the actions of serotonin and include nausea, gastric discomfort, vomiting, anorexia, diarrhea and skin hyperhydrosis. In addition, there is a risk of physical dependence and withdrawal with abrupt cessation of treatment with antidepressants. Furthermore, antidepressants typically interfere with sexual function and desire. Duloxetine was assessed for tolerability across five clinical trials of over 6 months in duration and the most common side effects included nausea, headache, dry mouth, insomnia, fatigue, constipation, diarrhea and dizziness (Choy et al., 2009) with about 20% of patients discontinuing due to adverse effects. Although milnacipran was generally well tolerated, approximately twice as patients in the treated groups withdrew from the study due to adverse effects including nausea, constipation, palpitations, and flushing compared to those in the placebo-treated group (Harris & Clauw, 2008).
Antiepileptic drugs including gabapentin and pregabalin have been prescribed to patients with neuropathic pain subtypes and fibromyalgia (Mease, 2005). Pregabalin was the first drug approved for fibromyalgia in 2007 by the FDA. Pregabalin has demonstrated efficacy in several recent fibromyalgia trials with improved pain scores, quality of sleep and fatigue (Kim et al., 2009). Common side effects of pregabalin included dizziness, sleepiness and weight gain. Less common side effects are difficulty concentrating and paying attention, dry mouth and blurred vision. Pregabalin is also a scheduled compound at Schedule V suggesting some potential for abuse and withdrawal symptoms. Thus, while pregabalin showed reduced pain in some patients, there is still room for improvement of both efficacy and side effect profile.
Other compounds that may be useful in treating fibromyalgia include monoamine oxidase inhibitors (i.e., pirlindole), 5-HT3 antagonists (i.e., tropisetron), opioids, tramadol, muscle relaxants, NMDA receptor antagonists and dopamine agonists (i.e., pramipexole) (Mease, 2005). Many of these compounds show either weak efficacy, less broad spectrum efficacy for symptoms or intolerable side-effect profiles included drug dependence.